Kidney and Hematopoietic Cell Transplants Using a Regimen to Promote Hematopoietic Cell Engraftment

NCT ID: NCT04571203

Last Updated: 2022-05-11

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-06
• Study Completion Date: 2029-10-01

Brief Summary

This is a single arm phase 1 non randomized dose finding study for safety, feasibility and efficacy of deceased donor vertebral body (VB) marrow cell infusion and kidney transplantation.

Detailed Description

Patients will undergo a standard of care deceased donor kidney transplant and thereafter the recipient will receive TLI (Total Lymphoid Irradiation)/single low dose Total Body Irradiation, ATG (Anti-Thymocyte Globulin) conditioning, followed by an infusion of whole bone marrow cells harvested from the same donor vertebral bodies. Patients will be receive standard of care doses of steroids, MMF and tacrolimus as part of their transplant immunosuppression.

Subjects will be withdrawn from the immunosuppression if they have met the withdrawal criteria.

Conditions

Immune Tolerance

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I Study of Combined DD Kidney and HCT Transplant

Single arm Phase 1 non randomized dose finding study for safety, feasibility and efficacy of deceased donor vertebral body (VB) marrow cell infusion

Group Type: EXPERIMENTAL

Combined Deceased Donor Kidney and Hematopoietic Cell Transplants

Intervention Type: BIOLOGICAL

This combined kidney and hematopoietic cell transplants with a conditioning regimen with irradiation and ATG creates an environment of immune-tolerance. This promotes hematopoietic cell engraftment.

Interventions

Combined Deceased Donor Kidney and Hematopoietic Cell Transplants

This combined kidney and hematopoietic cell transplants with a conditioning regimen with irradiation and ATG creates an environment of immune-tolerance. This promotes hematopoietic cell engraftment.

Intervention Type: BIOLOGICAL

Other Intervention Names

Radiation

Eligibility Criteria

Inclusion Criteria

1. Patient is ≥ 18 years old, and <65 years of age.

2. Has End Stage Renal Disease (ESRD) and is a de novo kidney transplant candidate part Stanford standard of care.

3. Listed with the Organ Procurement and Transplantation Network (OPTN) for deceased donor transplantation.

4. A serotypic (Human Leucocyte Antigen) HLA match with the donor of a least 1 locus in A, B or DR.

5. Males and females of reproductive potential who agree to practice a reliable form of contraception for at least 1 year post transplant.

6. Females have a negative serum pregnancy test.

7. Ability to understand and the willingness to sign a written informed consent document. Patients must have signed informed consent to participate in the trial.

8. No known contraindication to administration of rabbit ATG or low dose irradiation.

1. Brain dead donor aged ≥ 16 and ≤ 55

2. Organ Procurement Organization (OPO) consent for vertebral body procurement

3. Organ Procurement Organization consent for research

4. Projected cold ischemia time <24 hours.

Exclusion Criteria

1. Known allergy to rabbit protein.

2. History of malignancy with the exception of non melanoma skin malignancy.

3. Pregnant woman or nursing mother.

4. Body weight >90kg or BMI >35.

5. Evidence of HIV 1/2 antibody (Ab), HTLV 1 and HTLV 2 Ab (Human T-Lymphotropic Virus), Hepatitis B sAg (surface antigen), Hepatitis C Ab, or positive syphilis screen.

6. EBV (Epstein Bar Virus)Ab positive donor to EBV Ab negative recipient.

7. Active bacterial, viral or fungal infection defined as currently taking medication for the infection.

8. Leukopenia (white blood cell count < 3000/mm3) or thrombocytopenia (with a platelet count < 100,000/mm3).

9. Psychiatric disorder(s) or psychosocial circumstance(s) which in the opinion of the Stanford Transplant team caring for this potential patient would place the patient at an unacceptable risk.

10. Concern for alcohol or other substance abuse.

11. Kidney disease at high risk for post transplant recurrence: aHUS (atypical hemolytic- uremic syndrome) and C3 glomerulopathy

12. Panel reactive antibody (PRA) >80%.

13. Positive donor specific antibody (DSA).

14. Prior or combined organ transplant.

15. Patients with >5 pack year smoking history, smoking within 10 years of enrollment, or first degree relative with lung cancer.

1. History of malignancy with the exception of non melanoma skin malignancy.

2. History of autoimmune disease.

3. Known medical diagnosis of Zika virus infection within the prior 6 months, including post mortem screening.

4. Serological evidence of HIV, Hepatitis B (surface antigen positive), or Hepatitis C infection.

5. Evidence of systemic infection.

6. Kidney Donor Profile Index (KDPI) > 70%.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Stephan Busque

Professor of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert Lowsky, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Stephan Busque, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University

Palo Alto, California, United States

Countries

United States

References

Busque S, Scandling JD, Lowsky R, Shizuru J, Jensen K, Waters J, Wu HH, Sheehan K, Shori A, Choi O, Pham T, Fernandez Vina MA, Hoppe R, Tamaresis J, Lavori P, Engleman EG, Meyer E, Strober S. Mixed chimerism and acceptance of kidney transplants after immunosuppressive drug withdrawal. Sci Transl Med. 2020 Jan 29;12(528):eaax8863. doi: 10.1126/scitranslmed.aax8863.

Reference Type: BACKGROUND

PMID: 31996467 (View on PubMed)

Other Identifiers

57511

Identifier Type: -

Identifier Source: org_study_id